Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis

Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell dea...

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Main Authors:	Singh, P K, Kumar, A
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979429/

id	pubmed-4979429
recordtype	oai_dc
spelling	pubmed-49794292016-08-22 Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis Singh, P K Kumar, A Article Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Müller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Müller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis. Nature Publishing Group 2016-05-30 /pmc/articles/PMC4979429/ /pubmed/27551524 http://dx.doi.org/10.1038/cddiscovery.2016.34 Text en Copyright © 2016 Official Journal of the Cell Death Differentiation Association http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Singh, P K Kumar, A
spellingShingle	Singh, P K Kumar, A Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
author_facet	Singh, P K Kumar, A
author_sort	Singh, P K
title	Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
title_short	Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
title_full	Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
title_fullStr	Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
title_full_unstemmed	Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis
title_sort	mitochondria mediates caspase-dependent and independent retinal cell death in staphylococcus aureus endophthalmitis
description	Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Müller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Müller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979429/
_version_	1613624783694462976

Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis

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